Experimental study of the effects of N-linked glycans in influenza A hemagglutinin on antigenic diversification and immune escape

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17943
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Ushirogawa Hiroshi 川崎医科大学, 医学部, 助教 (00299182)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: インフルエンザウイルス / ヘマグルチニン / N型糖鎖 / 抗原性多様化 / 免疫逃避

Outline of Final Research Achievements

In influenza A virus, the surface glycoprotein hemagglutinin(HA) is known to be the primary target for neutralizing antibodies, in particular a set of canonical antigenic sites on the globular head of the molecule. The ability of influenza A to rapidly accumulate substitutions in HA is vital for its ability to escape from the immunological memory of its host, contributing to its seasonal impact on human health. In this study, we examined to what extent the N-linked glycans (N-glycans) in shielding antigenic sites of HA affect virus properties and neutralization escape using recombinant virus strains. As a result, it was suggested that the N-glycans are important factors that determine the viral properties and affect the neutralizing activity of the antibody. This research shown that focusing on the N-glycans in diversification of antigenicity may be a clue to improve the effect of the HA vaccine.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

インフルエンザワクチンはワクチン株と市中流行株の抗原性が一致せず、効果的な免疫を誘導できない場合が多い。特にA/香港型（H3N2亜型）インフルエンザウイルスは抗原変異頻度が高い性質を持つウイルスであり、2009年の新型インフルエンザウイルスによるパンデミック後に再流行したことを鑑みると、新型コロナウイルスパンデミック後の、インフルエンザに対する集団的な免疫力低下が懸念される状況下で再び大流行することも考えられる。これを阻止し、人々の健康被害拡大や経済的損失を防ぐためには、ワクチン効果の向上が極めて重要な課題であり、本研究成果はその課題解決に寄与する情報基盤として大きな意義を持つ。